WELLBUTRIN SR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for WELLBUTRIN SR (WELLBUTRIN SR).
Wellbutrin SR (bupropion) is an atypical antidepressant. Its mechanism of action is not fully understood, but it is thought to involve inhibition of dopamine and norepinephrine reuptake in the brain, with minimal effect on serotonin reuptake. It also acts as a nicotinic acetylcholine receptor antagonist.
| Metabolism | Extensively metabolized in the liver via CYP2B6, with hydroxybupropion as the major active metabolite. Minor pathways include CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4. |
| Excretion | Primarily renal (87% as bupropion and its metabolites, with 10% as unchanged drug); 10% fecal. |
| Half-life | Terminal half-life of bupropion is approximately 21 hours (±9 hours); for the active metabolite hydroxybupropion, half-life is ~20-27 hours. Steady state reached within 5-8 days. |
| Protein binding | 84% bound to plasma proteins (primarily albumin). |
| Volume of Distribution | Approximately 19-31 L/kg for bupropion; extensive tissue distribution. |
| Bioavailability | SR formulation: absolute bioavailability ~87% (due to extensive first-pass metabolism, bupropion itself has low systemic availability but active metabolites contribute). |
| Onset of Action | 2-4 weeks for therapeutic antidepressant effect; immediate-release peak plasma levels at 2 hours, sustained-release (SR) at 3 hours. |
| Duration of Action | Duration of clinical effect is 24 hours with SR formulation, allowing once-daily dosing; sustained action maintained by active metabolites. |
| Molecular Weight | 239.74 |
150 mg orally once daily, may increase to 150 mg twice daily after 3 days if needed. Maximum 300 mg/day.
| Dosage form | TABLET, EXTENDED RELEASE |
| Renal impairment | CrCl <30 mL/min: not recommended. CrCl 30-60 mL/min: reduce dose or increase interval (e.g., 150 mg every 48 hours). |
| Liver impairment | Child-Pugh Class B: reduce dose to 100 mg/day or 150 mg every other day. Class C: contraindicated. |
| Pediatric use | Not approved for pediatric use. Clinical trials insufficient to establish safety and efficacy in patients <18 years. |
| Geriatric use | Start at 150 mg daily; titrate slowly due to increased risk of seizures and comorbidities. Monitor renal function. |
| 1st trimester | Data limited; studies suggest increased risk of cardiovascular malformations, particularly ventricular septal defects, with first-trimester exposure. Risk-benefit assessment required. |
| 2nd trimester | No specific trimester-specific risks identified; monitor for maternal and fetal effects. Caution advised. |
| 3rd trimester | Use in third trimester may increase risk for neonatal complications including respiratory distress, feeding difficulties, and withdrawal symptoms. Weigh benefits against risks. |
Clinical note
Comprehensive clinical and safety monograph for WELLBUTRIN SR (WELLBUTRIN SR).
| Placental transfer | Bupropion crosses the placenta; cord blood levels are approximately 20-30% of maternal serum levels. |
| Breastfeeding | Bupropion and its metabolites are excreted into breast milk in low concentrations. Infant serum levels are low, but there have been reports of seizures in breastfed infants. Monitor infant for irritability, feeding issues, and seizures. Use with caution, especially if nursing a preterm or ill infant. |
■ FDA Black Box Warning
Antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thinking and behavior with antidepressant use in patients over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and older. All patients starting antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior.
| Serious Effects |
Seizure disorderCurrent or prior diagnosis of bulimia or anorexia nervosaAbrupt discontinuation of alcohol or sedativesConcomitant use of monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuationKnown hypersensitivity to bupropion
| Precautions | Seizure risk: dose-dependent; increased in patients with predisposing factors (e.g., head trauma, CNS tumor, eating disorders, abrupt discontinuation of alcohol/benzodiazepines)., Neuropsychiatric reactions (including suicidality, hostility, agitation) during smoking cessation., Hypertension: monitor blood pressure, especially in patients with pre-existing hypertension or those using nicotine replacement therapy., Activation of mania/hypomania in patients with bipolar disorder., Angle-closure glaucoma: may cause mydriasis., Hepatotoxicity: rare but reported., Serotonin syndrome when used with other serotonergic drugs. |
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| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | FDA Pregnancy Category B. First trimester: limited human data do not show increased risk of major congenital malformations overall; some studies suggest small increased risk of cardiovascular defects (e.g., ventricular septal defect) but not confirmed. Second and third trimesters: no specific malformation risk; may be associated with preterm birth and low birth weight. Neonatal effects: risk of neonatal withdrawal syndrome (irritability, feeding difficulties, respiratory depression) after late third-trimester exposure; no known risk of persistent pulmonary hypertension. |
| Fetal Monitoring | Monitor maternal blood pressure (bupropion may increase BP). Fetal ultrasound for growth and anatomy. Neonatal monitoring for withdrawal symptoms (irritability, feeding intolerance, respiratory distress) during first 48 hours. Assess for signs of neonatal toxicity if maternal dose >300 mg/day. |
| Fertility Effects | No known adverse effects on fertility in humans. Animal studies show no impairment. May improve sexual function in women with depression, potentially benefiting fertility indirectly. |
| Food/Dietary | No significant food interactions reported. However, taking with food may reduce nausea. Avoid high-fat meals as they may increase absorption rate. |
| Clinical Pearls | Wellbutrin SR (bupropion SR) has a lower risk of sexual dysfunction and weight gain compared to SSRIs. Avoid in patients with seizure disorders or eating disorders due to increased seizure risk. Titrate slowly to minimize side effects. Monitor for hypertension, especially in patients with pre-existing conditions. Do not exceed 400 mg/day for SR formulation. Use with caution in patients with hepatic impairment. |
| Patient Advice | Take at the same time each day with or without food. · Do not crush, break, or chew tablets; swallow whole. · Avoid alcohol to reduce seizure risk. · Report any new or worsening depression, suicidal thoughts, or unusual changes in mood. · May cause dry mouth, insomnia, headache, or nausea; these often improve over time. · Do not take with other medications containing bupropion. · Inform your doctor if you have a history of seizures, head injury, or eating disorders. |